This study of the mechanisms that are responsible for the development of hepatic and hypoxic encephalopathy will continue in the third year with studies of ammonia and short chain fatty acid metabolism by the brain. Preliminary data indicate that the blood-brain barrier permeability to ammonia, relative to water, is increased by 27 percent 12 weeks after portacaval shunt construction. We will continue our efforts to develop an adequate model of brain ammonia influx and glutamine efflux. Preliminary work using 11C-SCFA to assess BBB permeability will be continued. We will make use of our recently developed device to measure brain radioactivity serially under computer control. These data will be analyzed with computer solved metabolic and physiological models. We plan to start developmental studies in an attempt to model cerebral oxygen metabolism, again using our computerized device. We hope to study cerebral oxygen metabolism and blood flow under conditions of altered oxygen-hemoglobin affinity and hypoxia.